The long-term goals of our research are to: 1) help VA clinicians improve outcomes for veterans with chronic, hepatitis C virus (HCV) infections using treatment regimens that may incorporate newly available, directly acting antivirals (DAA); 2) provide information to policymakers considering the benefits, harms, and costs associated with these and forthcoming new treatment regimens; and 3) conduct research that responds directly to the most pressing questions delineated by VA clinician and operational leaders regarding HCV. Chronic HCV is of particular concern to the VHA given that 147,000 veterans are infected, the condition is difficult and extremely costly to manage, and causes decompensated cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Standard two-drug HCV treatments are effective in a limited proportion of patients and can cause substantial side effects. When added to standard treatment, DAAs improve success rates but are also expensive and increase rates of serious side effects. VA has estimated the expenditures for DAAs and associated treatments could reach one billion dollars in fiscal year 2012. In addition, recent studies provide evidence that an individual's Interleukin 28B (IL-28B) genotype predicts response to HCV therapy and may prove useful in helping predict response to therapy. We aim to study the costs, cost-effectiveness, and budgetary impact of alternative treatment regimens including DAAs. Our study has three specific aims: 1. To characterize the treatment costs and utilization, care patterns, and patient attributes of the VHA HCV population. a. We will analyze laboratory and pharmacy data from the VA Clinical Case Registry of HCV care, VA administrative datasets, and service costs from the VA's Health Economics Resource Center. 2. To assess the cost-effectiveness of DAAs and IL-28B genotype testing in the VHA HCV population, and to develop an analytic framework for evaluating the cost-effectiveness of additional new treatments for HCV. a. We will develop a VHA-specific cost-effectiveness model to evaluate how alternative HCV treatment regimens, including the new DAAs, and any additional new HCV drugs approved during the project period, influence long-term outcomes, including mortality, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. b. We will quantify differences in health improvements and changes in costs attributable to DAA and other new HCV drug use for subgroups of veterans defined in terms of combinations of age, extent of liver fibrosis, and IL-28B genotype. Subgroup differences may result from disease prognosis, other medical costs, and response to treatment which in turn may influence cost-effectiveness.. 3. To estimate the VA budget impact and resource requirements associated with uptake of the new treatment strategies. a. We will conduct budget impact and resource requirement analyses using the VHA-specific cost- effectiveness model and VA-specific inputs for uptake of new treatment regimens to assess all VA costs including inpatient care, outpatient care, including staffing, and pharmacy costs. We will develop a spreadsheet-based tool for direct use by VA policymakers to help them to anticipate and plan for the optimal roll-out and management of HCV treatments.